Azine-Hydrazone Tautomerism of Guanylhydrazones: Evidence for the Preference Toward the Azine Tautomer

Guanylhydrazones
have been known for a long time and have wide
applications in organic synthesis, medicinal chemistry, and material
science; however, little attention has been paid toward their electronic
and structural properties. Quantum chemical analysis on several therapeutically
important guanylhydrazones indicated that all of them prefer the azine
tautomeric state (by about 3–12 kcal/mol). A set of simple
and conjugated azines were designed using quantum chemical methods,
whose tautomeric preference toward the azine tautomer is in the range
of 3–8 kcal/mol. Twenty new azines were synthesized and isolated
in their neutral state. Variable temperature NMR study suggests existence
of the azine tautomer even at higher temperatures with no traces of
the hydrazone tautomer. The crystal structures of two representative
compounds confirmed that the title compounds prefer to exist in their
azine tautomeric form.